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Navigating the Fungal Polyketide Chemical Space: From Genes to Molecules
Open accessAbstract
The iterative type I polyketide synthases (IPKSs) are central to the biosynthesis of an enormously diverse array of natural products in fungi. These natural products, known as polyketides, exhibit a wide range of biological activities and include clinically important drugs as well as undesirable toxins. The PKSs synthesize these structurally diverse polyketides via a series of decarboxylative condensations of malonyl-CoA extender units and β-keto modifications in a highly programmed manner. Significant progress has been made over the past few years in understanding the biosynthetic mechanism and programming of fungal PKSs. The continuously expanding fungal genome sequence data have sparked genome-directed discoveries of new fungal PKSs and associated products. The increasing number of fungal PKSs that have been linked to their products along with in-depth biochemical and structural characterizations of these large enzymes have remarkably improved our knowledge on the molecular basis for polyketide structural diversity in fungi. This Perspective highlights the recent advances and examines how the newly expanded paradigm has contributed to our ability to link fungal PKS genes to chemical structures and vice versa. The knowledge will help us navigate through the logarithmically expanding seas of genomic information for polyketide compound discovery and provided opportunities to reprogram these megasynthases to generate new chemical entities.
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Metadata
- Authors
- Chooi, Y.-H., & Tang, Y.
- Venue
- The Journal of Organic Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2012-09-13
- Volume
- 77
- Issue
- 22
- Pages
- 9933-9953
- ISSN
- 0022-3263 (ISSN-L)
- 1520-6904
- OpenAlex
- W2040792095
- Cited by
- 271
- References
- 111
- FWCI
- 13.63
- Type
- journal article
- Language
- en
- Open access
- green
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.